Skip to main content
SpringerLink
Log in

Humans, Mice, and Mechanisms of Intestinal Atresias: A Window into Understanding Early Intestinal Development

  • Review Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

Intestinal atresias have long been hypothesized to result from either failure of recanalization of the intestinal lumen or in utero vascular accidents. Recent work in animal models is now calling for a reassessment of these widely held paradigms.

Purpose

In this review, we will examine the data that led to the original hypotheses and then evaluate more recent work challenging these hypotheses. Furthermore, we will discuss how defining the mechanism of atresia formation in animal models may provide insight into early intestinal development and the mechanism of lengthwise intestinal growth.

Conclusion

Such insight will be critical in developing regenerative therapies for patients with intestinal failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. International Clearinghouse for Birth Defects Surveillance and Research. Annual report 2007.

  2. Duodenal atresia and stenosis. In O’Neill JA Jr RM, Grosfeld JL, et al eds. Pediatric Surgery, Vol. 2. St Louis, Mo: Mosby, 1998.

  3. Tandler J. Zur Entwicklungsgeschichte des menschlichen Duodenum in fruhen Embryonalstadien. Morphol Jahrb 1900; 29:187.

    Google Scholar 

  4. Cheng W, Tam PK. Murine duodenum does not go through a “solid core” stage in its embryological development. Eur J Pediatr Surg 1998; 8(4):212–5.

    Article  PubMed  CAS  Google Scholar 

  5. Fairbanks TJ, Kanard R, Del Moral PM, et al. Fibroblast growth factor receptor 2 IIIb invalidation--a potential cause of familial duodenal atresia. J Pediatr Surg 2004; 39(6):872–4.

    Article  PubMed  Google Scholar 

  6. Kanard RC, Fairbanks TJ, De Langhe SP, et al. Fibroblast growth factor-10 serves a regulatory role in duodenal development. J Pediatr Surg 2005; 40(2):313–6.

    Article  PubMed  Google Scholar 

  7. Louw JH, Barnard CN. Congenital intestinal atresia; observations on its origin. Lancet 1955; 269(6899):1065–7.

    Article  PubMed  CAS  Google Scholar 

  8. Barnard CN. The genesis of intestinal atresia. Surg Forum 1957; 7:393–6.

    PubMed  CAS  Google Scholar 

  9. Barnard CN, Louw JH. The genesis of intestinal atresia. Minn Med 1956; 39(11):745; passim.

    PubMed  CAS  Google Scholar 

  10. Abdullah F, Arnold MA, Nabaweesi R, et al. Gastroschisis in the United States 1988–2003: analysis and risk categorization of 4344 patients. J Perinatol 2007; 27(1):50–5.

    Article  PubMed  CAS  Google Scholar 

  11. Stollman TH, Wijnen RM, Draaisma JM. Investigation for cystic fibrosis in infants with jejunoileal atresia in the Netherlands: a 35-year experience with 114 cases. Eur J Pediatr 2007; 166(9):989–90.

    Article  PubMed  Google Scholar 

  12. Roberts HE, Cragan JD, Cono J, et al. Increased frequency of cystic fibrosis among infants with jejunoileal atresia. Am J Med Genet 1998; 78(5):446–9.

    Article  PubMed  CAS  Google Scholar 

  13. Dalla Vecchia LK, Grosfeld JL, West KW, et al. Intestinal atresia and stenosis: a 25-year experience with 277 cases. Arch Surg 1998; 133(5):490–6; discussion 496–7.

    Article  PubMed  CAS  Google Scholar 

  14. Johnson SM, Meyers RL. Inherited thrombophilia: a possible cause of in utero vascular thrombosis in children with intestinal atresia. J Pediatr Surg 2001; 36(8):1146–9.

    Article  PubMed  CAS  Google Scholar 

  15. Greer FR (2010) Vitamin K the basics—What’s new? Early Hum Dev. 86:43–47

    Article  PubMed  Google Scholar 

  16. Bowen DJ, Bowley S, John M, Collins PW. Factor V Leiden (G1691A), the prothrombin 3′-untranslated region variant (G20210A) and thermolabile methylenetetrahydrofolate reductase (C677T): a single genetic test genotypes all three loci--determination of frequencies in the S. Wales population of the UK. Thromb Haemost 1998; 79(5):949–54.

    PubMed  CAS  Google Scholar 

  17. Arruda VR, Annichino-Bizzacchi JM, Costa FF, Reitsma PH. Factor V Leiden (FVQ 506) is common in a Brazilian population. Am J Hematol 1995; 49(3):242–3.

    Article  PubMed  CAS  Google Scholar 

  18. Asindi AA, Al-Daama SA, Zayed MS, Fatinni YA. Congenital malformation of the gastrointestinal tract in Aseer region, Saudi Arabia. Saudi Med J 2002; 23(9):1078–82.

    PubMed  Google Scholar 

  19. Frances F, Portoles O, Gabriel F, et al. [Factor V Leiden (G1691A) and prothrombin-G20210A alleles among patients with deep venous thrombosis and in the general population from Spain]. Rev Med Chil 2006; 134(1):13–20.

    PubMed  CAS  Google Scholar 

  20. Garcia-Gala JM, Alvarez V, Pinto CR, et al. Factor V Leiden (R506Q) and risk of venous thromboembolism: a case-control study based on the Spanish population. Clin Genet 1997; 52(4):206–10.

    Article  PubMed  CAS  Google Scholar 

  21. Gibson CS, MacLennan AH, Rudzki Z, et al. The prevalence of inherited thrombophilias in a Caucasian Australian population. Pathology 2005; 37(2):160–3.

    Article  PubMed  CAS  Google Scholar 

  22. Hepner M, Roldan A, Pieroni G, et al. Factor V Leiden mutation in the Argentinian population. Thromb Haemost 1999; 81(6):989.

    PubMed  CAS  Google Scholar 

  23. Herrmann FH, Koesling M, Schroder W, et al. Prevalence of factor V Leiden mutation in various populations. Genet Epidemiol 1997; 14(4):403–11.

    Article  PubMed  CAS  Google Scholar 

  24. Hudecek J, Dobrotova M, Hybenova J, et al. [Factor V Leiden and the Slovak population]. Vnitr Lek 2003; 49(11):845–50.

    PubMed  CAS  Google Scholar 

  25. McCowan LM, Craigie S, Taylor RS, et al. Inherited thrombophilias are not increased in “idiopathic” small-for-gestational-age pregnancies. Am J Obstet Gynecol 2003; 188(4):981–5.

    Article  PubMed  Google Scholar 

  26. Nurk E, Tell GS, Refsum H, et al. Factor V Leiden, pregnancy complications and adverse outcomes: the Hordaland Homocysteine Study. QJM 2006; 99(5):289–98.

    Article  PubMed  CAS  Google Scholar 

  27. Palomo I, Pereira J, Alarcon M, et al. [Factor V Leiden and prothrombin G20210A among Chilean patients with venous and arterial thrombosis]. Rev Med Chil 2005; 133(12):1425–33.

    PubMed  Google Scholar 

  28. Pecheniuk NM, Marsh NA, Walsh TP. Multiple analysis of three common genetic alterations associated with thrombophilia. Blood Coagul Fibrinolysis 2000; 11(2):183–9.

    PubMed  CAS  Google Scholar 

  29. Zoller B, Norlund L, Leksell H, et al. High prevalence of the FVR506Q mutation causing APC resistance in a region of southern Sweden with a high incidence of venous thrombosis. Thromb Res 1996; 83(6):475–7.

    Article  PubMed  CAS  Google Scholar 

  30. Balogh I, Poka R, Pfliegler G, et al. High prevalence of factor V Leiden mutation and 20210A prothrombin variant in Hungary. Thromb Haemost 1999; 81(4):660–1.

    PubMed  CAS  Google Scholar 

  31. Clark P, Walker ID, Govan L, et al. The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes. Br J Haematol 2008; 140(2):236–40.

    PubMed  Google Scholar 

  32. Dizon-Townson DS, Meline L, Nelson LM, et al. Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction. Am J Obstet Gynecol 1997; 177(2):402–5.

    Article  PubMed  CAS  Google Scholar 

  33. Jaaskelainen E, Toivonen S, Romppanen EL, et al. M385T polymorphism in the factor V gene, but not Leiden mutation, is associated with placental abruption in Finnish women. Placenta 2004; 25(8–9):730–4.

    Article  PubMed  CAS  Google Scholar 

  34. Kobashi G, Kato EH, Morikawa M, et al. MTHFR C677T Polymorphism and factor V Leiden mutation are not associated with recurrent spontaneous abortion of unexplained etiology in Japanese women. Semin Thromb Hemost 2005; 31(3):266–71.

    Article  PubMed  CAS  Google Scholar 

  35. Lee DH, Henderson PA, Blajchman MA. Prevalence of factor V Leiden in a Canadian blood donor population. CMAJ 1996; 155(3):285–9.

    PubMed  CAS  Google Scholar 

  36. Prochazka M, Lubusky M, Slavik L, et al. Frequency of selected thrombophilias in women with placental abruption. Aust N Z J Obstet Gynaecol 2007; 47(4):297–301.

    Article  PubMed  Google Scholar 

  37. Saour JN, Shoukri MM, Mammo LA. The Saudi Thrombosis and Familial Thrombophilia Registry. Design, rational, and preliminary results. Saudi Med J 2009; 30(10):1286–90.

    PubMed  Google Scholar 

  38. Sottilotta G, Mammi C, Furlo G, et al. High incidence of factor V Leiden and prothrombin G20210A in healthy southern Italians. Clin Appl Thromb Hemost 2009; 15(3):356–9.

    Article  PubMed  Google Scholar 

  39. Vaughan J, Power C, Nolan C, et al. The incidence of factor V Leiden in a normal Irish population and its relationship to the laboratory diagnosis of APC resistance. Thromb Haemost 1999; 81(4):661–3.

    PubMed  CAS  Google Scholar 

  40. Batalla A, Alvarez R, Reguero JR, et al. Synergistic effect between apolipoprotein E and angiotensinogen gene polymorphisms in the risk for early myocardial infarction. Clin Chem 2000; 46(12):1910–5.

    PubMed  CAS  Google Scholar 

  41. Berthier MT, Houde A, Bergeron J, et al. Effect of the factor VII R353Q missense mutation on plasma apolipoprotein B levels: impact of visceral obesity. J Hum Genet 2003; 48(7):367–73.

    Article  PubMed  CAS  Google Scholar 

  42. Bowman R, Joosen AM, Welch AA, et al. Factor VII, blood lipids and fat intake: gene-nutrient interaction and risk of coronary heart disease with the factor VII R353Q polymorphism. Eur J Clin Nutr 2009; 63(6):771–7.

    Article  PubMed  CAS  Google Scholar 

  43. Di Castelnuovo A, D’Orazio A, Amore C, et al. Genetic modulation of coagulation factor VII plasma levels: contribution of different polymorphisms and gender-related effects. Thromb Haemost 1998; 80(4):592–7.

    PubMed  Google Scholar 

  44. Eriksson-Berg M, Deguchi H, Hawe E, et al. Influence of factor VII gene polymorphisms and environmental factors on plasma coagulation factor VII concentrations in middle-aged women with and without manifest coronary heart disease. Thromb Haemost 2005; 93(2):351–8.

    PubMed  CAS  Google Scholar 

  45. Lindman AS, Pedersen JI, Arnesen H, et al. Coagulation factor VII, R353Q polymorphism, and serum choline-containing phospholipids in males at high risk for coronary heart disease. Thromb Res 2004; 113(1):57–65.

    Article  PubMed  CAS  Google Scholar 

  46. Kakko S, Elo T, Tapanainen JM, et al. Polymorphisms of genes affecting thrombosis and risk of myocardial infarction. Eur J Clin Invest 2002; 32(9):643–8.

    Article  PubMed  CAS  Google Scholar 

  47. Doggen CJ, Manger Cats V, Bertina RM, et al. A genetic propensity to high factor VII is not associated with the risk of myocardial infarction in men. Thromb Haemost 1998; 80(2):281–5.

    PubMed  CAS  Google Scholar 

  48. Heywood DM, Carter AM, Catto AJ, et al. Polymorphisms of the factor VII gene and circulating FVII:C levels in relation to acute cerebrovascular disease and poststroke mortality. Stroke 1997; 28(4):816–21.

    PubMed  CAS  Google Scholar 

  49. Mrozikiewicz PM, Cascorbi I, Ziemer S, et al. Reduced procedural risk for coronary catheter interventions in carriers of the coagulation factor VII-Gln353 gene. J Am Coll Cardiol 2000; 36(5):1520–5.

    Article  PubMed  CAS  Google Scholar 

  50. Nishiuma S, Kario K, Nakanishi K, et al. Factor VII R353Q polymorphism and lacunar stroke in Japanese hypertensive patients and normotensive controls. Blood Coagul Fibrinolysis 1997; 8(8):525–30.

    Article  PubMed  CAS  Google Scholar 

  51. Perveen R, Lloyd IC, Clayton-Smith J, et al. Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations. Invest Ophthalmol Vis Sci 2000; 41(9):2456–60.

    PubMed  CAS  Google Scholar 

  52. Eggenschwiler J, Ludwig T, Fisher P, et al. Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes. Genes Dev 1997; 11(23):3128–42.

    Article  PubMed  CAS  Google Scholar 

  53. Rice R, Spencer-Dene B, Connor EC, et al. Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate. J Clin Invest 2004; 113(12):1692–700.

    PubMed  CAS  Google Scholar 

  54. Riley BM, Mansilla MA, Ma J, et al. Impaired FGF signaling contributes to cleft lip and palate. Proc Natl Acad Sci U S A 2007; 104(11):4512–7.

    Article  PubMed  CAS  Google Scholar 

  55. Riley BM, Schultz RE, Cooper ME, et al. A genome-wide linkage scan for cleft lip and cleft palate identifies a novel locus on 8p11-23. Am J Med Genet A 2007; 143A(8):846–52.

    Article  PubMed  CAS  Google Scholar 

  56. Conrad C, Freitas A, Clifton MS, Durham MM Hereditary multiple intestinal atresias: 2 new cases and review of the literature. J Pediatr Surg 2010; 45(4):E21–4.

    Article  PubMed  Google Scholar 

  57. Pameijer CR, Hubbard AM, Coleman B, Flake AW. Combined pure esophageal atresia, duodenal atresia, biliary atresia, and pancreatic ductal atresia: prenatal diagnostic features and review of the literature. J Pediatr Surg 2000; 35(5):745–7.

    Article  PubMed  CAS  Google Scholar 

  58. Nijmeijer RM, Leeuwis JW, DeLisio A, et al. Visceral endoderm induces specification of cardiomyocytes in mice. Stem Cell Res 2009; 3(2–3):170–8.

    Article  PubMed  Google Scholar 

  59. Fairbanks TJ, Kanard RC, De Langhe SP, et al. A genetic mechanism for cecal atresia: the role of the Fgf10 signaling pathway. J Surg Res 2004; 120(2):201–9.

    Article  PubMed  CAS  Google Scholar 

  60. Fairbanks TJ, Kanard RC, Del Moral PM, et al. Colonic atresia without mesenteric vascular occlusion. The role of the fibroblast growth factor 10 signaling pathway. J Pediatr Surg 2005; 40(2):390–6.

    Article  PubMed  Google Scholar 

  61. Fairbanks TJ, Sala FG, Kanard R, et al. The fibroblast growth factor pathway serves a regulatory role in proliferation and apoptosis in the pathogenesis of intestinal atresia. J Pediatr Surg 2006; 41(1):132–6; discussion 132–6.

    Article  PubMed  Google Scholar 

  62. Ornitz DM, Itoh N. Fibroblast growth factors. Genome Biol 2001; 2(3):3005:1–9.

    Google Scholar 

  63. Ramalho-Santos M, Melton DA, McMahon AP. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 2000; 127(12):2763–72.

    PubMed  CAS  Google Scholar 

  64. Gao N, White P, Kaestner KH. Establishment of intestinal identity and epithelial-mesenchymal signaling by Cdx2. Dev Cell 2009; 16(4):588–99.

    Article  PubMed  CAS  Google Scholar 

  65. Martinovic-Bouriel J, Bernabe-Dupont C, Golzio C, et al. Matthew-Wood syndrome: report of two new cases supporting autosomal recessive inheritance and exclusion of FGF10 and FGFR2. Am J Med Genet A 2007; 143(3):219–28.

    PubMed  Google Scholar 

  66. Mo R, Kim JH, Zhang J, et al. Anorectal malformations caused by defects in sonic hedgehog signaling. Am J Pathol 2001; 159(2):765–74.

    Article  PubMed  CAS  Google Scholar 

  67. FitzSimmons J, Chinn A, Shepard TH. Normal length of the human fetal gastrointestinal tract. Pediatr Pathol 1988; 8(6):633–41.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Silke Niederhaus for her translation of J. Tandler’s original publication and Anastasia Lopukhin for her assistance in editing this manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue H4/785c CSC, Madison, WI, 53792, USA

    Peter F. Nichol, Amy Reeder & Robert Botham

Authors
  1. Peter F. Nichol
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amy Reeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Botham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter F. Nichol.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nichol, P.F., Reeder, A. & Botham, R. Humans, Mice, and Mechanisms of Intestinal Atresias: A Window into Understanding Early Intestinal Development. J Gastrointest Surg 15, 694–700 (2011). https://doi.org/10.1007/s11605-010-1400-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-010-1400-y

Keywords

Search

Navigation